Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver () for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

中文翻译：

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全面整合单细胞 RNA 和转录组 RNA 测序，建立焦亡相关特征，改善胃癌的预后预测

细胞焦亡是一种以炎症小体为特征的 Gasdermin 依赖性程序性细胞死亡，在严重威胁人类健康的胃癌 (GC) 中发挥着复杂而动态的作用。因此，焦亡相关基因（PRG）作为患者预后生物标志物和治疗指标的价值需要在GC中得到开发。本研究整合了单细胞RNA测序（scRNA-seq）数据集GSE183904和TCGA数据库中的GC转录组数据，重点研究单细胞水平上GC中PRG的表达和分布。PRG 的预后特征是通过 Cox 和 LASSO 分析建立的。分析评价两组长期预后、免疫浸润、突变谱、CD274及化疗药物反应的差异。使用组织阵列验证 6 个 PRG、CD274、CD163 和 FoxP3 的表达。成功筛选出C12orf75、VCAN、RGS2、MKNK2、SOCS3和TNFAIP2，建立有效预测GC患者生存时间的特征。基于此签名开发了用于 GC 患者预后预测的网络服务器 ()。高风险评分患者通常预后较差，对经典化疗有抵抗力，肿瘤微环境更具免疫抑制性。VCAN、TNFAIP2 和 SOCS3 在 GC 中显着升高，而 RGS2 和 MKNK2 在肿瘤样本中降低。此外，VCAN 与 GC TME 中的 Tregs 和 M2 TAM 以及肿瘤细胞中的 CD274 的浸润呈正相关。总之，建立了有效的焦亡相关特征来准确预测GC患者的生存时间和治疗反应。